Therapeutic angiogenesis, i.e. use of growth factors to stimulate new blood vessel formation in areas of atherosclerotic damage, is one of the most promising new approaches to treatment of cardiovascular disease, the leading cause of morbidity and mortality in the US. Scatter factor or hepatocyte growth factor (SF/HGF) is a pleiotropic cytokine that has significant angiogenic activity in vitro and in vivo and may be a good candidate for therapeutic use. The project proposed will evaluate the feasibility of using SF/HGF gene transfer to stimulate angiogenesis in rat models of myocardial and peripheral ischemia. The specific aims are 1) to construct new SF/HGF vectors for use in gene therapy experiments; 2) to test whether direct injection of these vectors results in SF/HGF expression in ischemic tissue; and 3) to determine if SF/HGF gene transfer induces angiogenesis in vivo. Successful completion of the proposed studies will lead to confirmatory experiments in larger animals and clinical studies of SF/HGF gene therapy. PROPOSED COMMERCIAL APPLICATION: Angion Biomedica plans to submit a Phase II proposal to support studies of SF/HGF gene transfer in large animal models and the toxicology studies required before initiating clinical trails. The company expects to pursue clinical development of SF/HGF gene transfer in collaboration with a pharmaceutical industry partner. Angion Biomedica Corp. has signed a technology transfer agreement with North Shore University Hospital that includes an exclusive license for a pending patent covering therapeutic use of SF/HGF to induce angiogenesis. The overall goal is to develop a safe, reliable therapeutic approach for including neovascularization in patients with cardiovascular disease.